Learn / Metabolism
Metabolic pathways
Every FMK pathway as a clickable map. Pick one pathway to hammer it — next step, enzyme, regulator, cofactor, and the facts that get tested (NADPH and who needs it, rate-limiting steps, deficiencies) — or set it to all pathways for a mixed drill. Every answer says which enzyme and which pathway.
MEOS — microsomal ethanol-oxidizing system (CYP2E1)
NAPQI — toxic electrophile
Made from Acetaminophen (standard dose) by CYP2E1 (minor route normally — the major route once induced)
CYP2E1 (minor route normally — the major route once induced) · irreversible — MEOS — microsomal ethanol-oxidizing system (CYP2E1)
Cofactors: NADPH, O₂
Deficiency: Acetaminophen hepatotoxicity — a therapeutic dose in a chronic drinker: nausea and RUQ pain at 24 h, then AST/ALT in the thousands, ↑INR and encephalopathy at 72–96 h
Normally ~5% of a dose; most acetaminophen is glucuronidated and sulfated. Induction shifts the split.
Condition cards:Acetaminophen hepatotoxicity in chronic alcohol use (CYP2E1/NAPQI) →
Becomes Glutathione conjugate → mercapturate in urine via Glutathione S-transferase conjugation
Glutathione S-transferase conjugation — MEOS — microsomal ethanol-oxidizing system (CYP2E1)
The safe exit. Capacity is set by the hepatic glutathione reserve, which chronic alcohol use and poor nutrition have already lowered.
Becomes Centrilobular necrosis → acute liver failure via Once glutathione is exhausted, NAPQI binds cell proteins
Once glutathione is exhausted, NAPQI binds cell proteins — MEOS — microsomal ethanol-oxidizing system (CYP2E1)
Centrilobular (zone III) — that is where CYP2E1 lives. The double hit in a chronic drinker: more NAPQI made AND less glutathione to mop it up.